Canine infectious respiratory disease (CIRD) is a highly contagious disease common in dogs housed in crowded conditions such as re-homing centres and boarding or training kennels. Many dogs suffer only from a mild cough and recover after a short time, however in some cases a severe bronchopneumonia can develop (Appel and Binn, 1987). CIRD is rarely fatal but it delays re-homing of dogs at rescue centres and it causes disruption of schedules in training kennels as well as considerable treatment costs.
The pathogenesis of CIRD is considered to be multifactorial, involving several viruses and bacteria. The infectious agents considered to be the major causative pathogens of CIRD are canine parainfluenzavirus (CPIV) (Binn et al, 1967), canine adenovirus type 2 (CAV-2) (Ditchfield et al, 1962), and canine herpesvirus (CHV) (Karpas et al, 1968a and 1986b), canine respiratory coronavirus (CRCV) (WO 2004/011651 (The Royal Veterinary College) and Erles et al, 2003) and the bacterium Bordetella bronchiseptica (B. bronchiseptica) (Bemis et al, 1977a, Keil et al, 1998).
These viruses and bacterium have frequently been isolated during outbreaks and have been shown to cause respiratory symptoms or lung lesions in experimental infections (Appel and Percy 1970, Swango et al, 1970, Karpas et al, 1986b).
Also, human reovirus and mycoplasma species have been isolated from dogs with symptoms of CIRD (Lou and Wenner 1963, Randolph et al, 1993) Additional factors like stress may also be important.
B. bronchiseptica was reported as being a primary etiological agent in the respiratory disease “kennel cough” (Bemis et al, 1977b and Thompson et al, 1976). It predisposes dogs to the influence of other respiratory agents and frequently exists concurrently with them. Kennel cough can be reproduced by challenge with virulent B. bronchiseptica. Further, environmental factors such as cold, drafts, and high humidity, often typical conditions in dog kennels, increase susceptibility to the disease (Ellis et al, 2001). Antibiotics are generally recognised as poor agents to treat the primary disease (Ellis et al, 2001). In contrast, immunoprophylaxis for B. bronchiseptica provides a relatively effective means to aid in the control of disease.
The outstanding sign of B. bronchiseptica infection is a harsh, dry cough, which is aggravated by activity or excitement. The coughing occurs in paroxysms, followed by retching or gagging in attempts to clear small amounts of mucus from the throat. Body temperature may be elevated as secondary bacterial invasion takes place. Because kennel cough is highly contagious, the disease can readily be transmitted to susceptible dogs and produce a severe cough. The most severe signs are noted beginning two to five days following infection, but can continue for extended periods. Stress, particularly of adverse environmental conditions, may cause relapse during later stages of the disease.
Kennel cough is typically a condition of the upper airways and is characterised by nasal discharge and coughing. Whereas kennel cough mainly involves upper respiratory tract changes, the pathology of CIRD indicates that it is involved in lung damage and, in some cases, bronchopneumonia. Kennel cough is a milder syndrome than CIRD and does not have the wide range of pathology noted in CIRD. CIRD is also distinguished by an increased severity and mortality.
CIRD is a syndrome in dogs which present with respiratory signs ranging from mild to fatal disease. It is characterised by involvement of upper and lower airway infection with progression from inflammatory to exudative, oedematous and sometimes haemorrhagic pathology which can be widespread within the lung tissues. CIRD can also occur in the absence of B. bronchiseptica, and indeed some dogs contract CIRD whilst having no detectable B. bronchiseptica, which indicates that kennel cough and CIRD are distinct infections.
We have also confirmed the association of B. bronchiseptica with respiratory disease while concluding that other agents are involved in respiratory disease (Chalker et al, 2003).
We have now shown that Streptococcus equi sub species zooepidemicus (see Example 1), Mycoplasma cynos (see Example 2), and a Chlamydophila (see Example 3) are associated with CIRD. As all the dogs in our study populations were vaccinated against CPIV and CAV-2, we have no new data to support the involvement of these viruses in CIRD. However we have also found an increased prevalence of canine herpesvirus in dogs with more severe respiratory symptoms (see Example 4).
Streptococcus equi sub species zooepidemicus (S. zooepidemicus) is an opportunist pathogen which is frequently isolated from a variety of animal hosts, not only from horses. It is often found as a commensal of the upper respiratory tract mucosa of mammals (Timoney et al, 1988; Quinn et al, 1999) and has been associated with several disease syndromes including lower airway disease, foal pneumonia and cervicitis in horses (Chanter, 1997; Biberstein and Hirsh, 1999), pneumonia in llamas (Biberstein and Hirsh, 1999), septicaemia and arthritis in pigs (Timoney, 1987), mastitis in cows and goats (Timoney et al, 1988), septicaemia in poultry, pericarditis and pneumonia in lambs (Timoney, 1987), lymphadenitis in guinea pigs (Quinn et al, 1999), glomerulonephritis in humans (Balter et al, 2000) and meningitis in humans (Ural et al, 2003). In dogs S. zooepidemicus has been associated with wound infections and septicaemia (Quinn et al, 1999) and acute necrotising haemorrhagic pneumonia (Garnett et al, 1982).
Although dogs in the latter stages of hemorrhagic streptococcal pneumoniae (HSP) share some histological features with dogs with CIRD, this is not the case in its early stages (see Chalker et al, 2003) and septic thrombi are present in HSP (Garnett et al, 1982). HSP has a rapid onset that was fatal in most cases without clinical signs, whereas with CIRD we see a slow onset with a huge range of clinical signs from nasal discharge, coughing, sneezing, retching, inappetance, pneumonia and bronchopneumonia.
Mycoplasma cynos (M. cynos) has been associated with canine urinary tract infection (Jang et al, 1984). It has also been identified in the lungs of a dog with distemper (Rosendal, 1978), and endobronchial inoculation of M. cynos was found to induce pneumonia in dogs (Rosendal & Vinther, 1977).
The canine distemper described by Rosendal (1978) is a complex disease following infection with canine distemper virus, various mycoplasma species and the bacterium Pseudomonas. This is a powerful combination of microbial challenges and, not surprisingly, results in pneumonia. The proportion of pathology due to the Mycoplasma spp. was not clear. Subsequent challenge with M. cynos was characterised by no signs of illness in the dogs although some local small inflammatory lesions were noted in 4 out of the 5 dogs inoculated. The significance of M. cynos in this syndrome was, as Rosendal stated, “difficult to assess”.
The Chlamydophila species associated with CIRD is very closely related to Chlamydophila abortus (C. abortus) by comparison of a 218 nucleotide sequence in the 23 S rRNA gene. The nucleotide sequence of this region in this Chlamydophila species (SEQ ID NO: 1) is over 99% identical to that of C. abortus, 98.6% identical to Chlamydophila psittaci and 96.3% identical to Chlamydophila felis. 
The Chlamydophila species was identified in the trachea and lungs of dogs with CIRD. By contrast, infection with C. abortus is typically associated with reproductive disorders, often leading to unwanted abortion, especially in sheep. C. abortus has not previously been described as having a role in respiratory infection in dogs.
There are very few publications regarding Chlamydiae species infecting dogs, and therefore very little is known of the biodiversity of canine Chlamydiae species. Recently, Chlamydia pneumoniae (C. pneumoniae) has been associated with athrosclerosis in dogs (Sako et al, 2002). An unidentified Chlamydophila spp has also been identified in a dog with septic polyarthritis (Lambrechts et al, 1999).
C. psittaci has previously been isolated from faeces, brain, liver, spleen, kidney and lung tissue of household dogs (Arizmendi et al, 1992; Fraser et al, 1985 and Gresham et al, 1996). Studies have demonstrated that 20% of the pet canine population in Germany and 10% in Japan have been exposed to and raised antibodies to Chlamydiaceae (Werth et al, 1987 and Fukushi et al, 1985). The prevalence of C. psittaci seropositive dogs in the UK is unknown (Gresham et al, 1996.). Dogs infected with C. psittaci may develop sub-clinical chronic infections, athrosclerosis, arthritis, conjunctivitis or even respiratory disease (Gresham et al, 1996 and Storz 1988). Gresham et al, (1996) isolated C. psittaci from a dog with symptoms of respiratory disease although these symptoms were not as severe as those in CIRD. It has been suggested that dogs may be potential reservoirs and, thereby, important in the epidemiology of human Chlamydiae infections (Gresham et al, 1996; Werth 1989). There is only one documented case of isolation in cell culture of C. psittaci from a naturally infected dog (Arizmendi et al, 1992), and one case of isolation from experimentally infected dogs (Young et al, 1972).
Vaccines are available against some of the infectious agents associated with CIRD, namely B. bronchiseptica as well as CPIV and CAV-2. However, despite the use of these vaccines, CIRD is still prevalent in kennels world-wide, which is possibly due to the vaccines not providing protection against all the infectious agents involved in CIRD.